Micro-organism reducing device

ABSTRACT

The invention relates to a microorganism reducing device, comprising a radiation device which is provided with a light source, a photosensitive substance which treats the area to be treated and is irradiated by said light source. The aim of said invention is to configure said device in such a way that it is possible to carry out an efficient and controllable treatment by means of operationally low-cost and easily handling apparatus. For this purpose, the inventive device comprises at least one applicator provided with a fibre-optic waveguide. In addition, the applicator and radiation device respectively comprise corresponding connector bodies coupling the applicator and radiation device in such a way that the light from the light source is emitted towards the treated area by means of the fibre-optic waveguide.

REFERENCE TO RELATED APPLICATION

This is a divisional application of Ser. No. 10/558,453, filed Dec. 22,2006. The subject matter of the aforementioned prior application ishereby incorporated herein by reference.

BACKGROUND OF THE INVENTION

The invention relates to an arrangement for reducing microorganisms. Theinvention furthermore relates to the use of such an arrangement fortherapy, in particular in the mouth, jaw, and facial area.

Known from WO 01/87416 A1 is such an arrangement and a method forreducing or destroying microorganisms, such as bacteria, using alight-activatable substance and photodynamic therapy (PDT). Using thelight-activatable substance, in particular a stain, the microorganismsare sensitized and/or stained, and they are killed using irradiationwith light of an appropriate wavelength and energy density as a resultof the selective action and/or staining. The principle of action of PDTis based on the physical effect of energy transmission to thelight-activatable substance, which is also called a photosensitizer.From there, the energy for reactions can be made available on the cellmembrane. The energy produced by means of a radiation device, especiallya laser device, is thus concentrated on the microorganisms and theequilibrium of reactions that also occur in the non-irradiated “normal”milieu are shifted and as a consequence the microorganisms aredestroyed.

Furthermore known from EP 0 637 976 B1 is the use of a light-sensitizingsubstance or compound or photosensitizer (PS) during production of amedication for use during disinfection or sterilization of tissues inthe oral cavity or a wound or lesion in the oral cavity by destroyingmicrobes in a periodontal pocket that are associated with an illness, inthe region between the tooth and the gum. The tissue, wound, or lesionis contacted with the photosensitizer, the microbes associated with theillness absorbing the photosensitizer. The tissue, wound, or lesion isirradiated with laser light at a wavelength absorbed by thephotosensitizer. The reduction in germs in this combined stain and lasertreatment is described for various germs and photosensitizers in theform of solutions with, among other things, methylene blue and toluidineblue in various fairly low concentrations, specifically from 0.01 to0.00125% (weight per volume), whereby furthermore the effect of theenergy density applied is indicated. HeNe lasers with a wavelength of634 nm and an output of 7.3 mW and GaAs lasers with a wavelength of 660nm and an output of 11 mW are used as light sources.

BRIEF SUMMARY OF THE INVENTION

Starting at this point, the underlying object of the invention is toembody the arrangement such that effective and controllable therapy isattained with an apparatus that is not very complex and with simplehandling. The therapy for local, superficial infections, especially inthe mouth, jaw, and facial area, should not be complex and should behighly functional. Moreover, the most homogeneous possible irradiationof the area to undergo therapy, in particular the surface of the oralmucosa, should be attained. With respect to the great distribution andgreat frequency of infections, especially in the area of the mouth, jaw,and face, including dentogenic infections, the problems that haveexisted in the past should be avoided or at least reduced.

Using a simple structure and simple handling, the inventive arrangementfacilitates functional and practical application of the therapy by meansof a light-activatable substance and a radiation device. Thelight-activatable substance is prepared in solution in a highconcentration, usefully filled in a syringe sterilized and ready to use.Advantageously, the concentration of the photosensitizer is provided ina solvent such as an aqueous solution or alcohol or ethanol, with a highvalue. The concentration, specifically weight per volume, isadvantageously greater than 0.1%, usefully greater than 0.5%, wherebythe upper limit is advantageously 10%, usefully 5%, especially 3%. Aconcentration of at least approximately 1% has proved to be particularlysuitable. The radiation device, which is in particular embodied as alaser device, is combined with an application system, wherebyapplicators can preferably be detachably connected to the radiationdevice. The applicators are advantageously single-use optics by means ofwhich it is possible to irradiate the area to undergo therapy in atargeted and precise manner. The applicators are used only once fortreatment so that in particular hygiene requirements are met andundesired transmission of microorganisms is safely avoided withoutcomplex measures for any subsequent or repeated sterilization. Theapplicators contain light conductors, in particular optical fibers, andenable without any problem intraoral light distribution and/orirradiation and can be embodied as pocket probes or surface probes. Theradiation device and the at least one applicator are preferably embodiedsuch that the light from the light source can be coupled directly intothe light conductor. In one preferred embodiment of the invention, alight conductor or an optical fiber with a high numerical aperture isused, whereby the numerical aperture is preferably greater than 0.5, inparticular greater than 0.7. Because of this, there are low losses whenthe light is coupled into the applicator or light conductor and at thesame time it is assured that the light beam exiting the applicator orlight conductor opens up.

In one preferred embodiment of the invention, a blocking device iscombined with the radiation device such that light cannot exit from theradiation device unless the applicator and/or light conductor isconnected. As long as the applicator is not properly connected to theradiation device, the blocking device prevents light from exitingdirectly out of the radiation device. In one preferred embodiment, theradiation device, in particular its head part, contains a preferablycentral bore into which the light conductor end of the applicator isinserted and fixed. The blocking device is especially arranged in thebeam path of the light from the light source and in the free end and/orin the free end face of the light conductor end. In accordance with theinvention, the blocking device is actuated when the applicator isconnected and/or when the light conductor end is inserted into theaforesaid bore, such that the beam path is uncovered, in particular bymeans of the light conductor end. The aforesaid bore and/or the insertedlight conductor end are arranged and/or aligned with respect to thelight source such that the light from the light source falls on the freeend face of the light conductor end, where necessary focused by means ofan optical system. The applicators contain a connecting or plug-inapparatus, in particular in the form of a Luer plug, for being receivedon a head or head part of the radiation device. Furthermore, theapplicators are embodied in an advantageous manner at least partiallycurved such that targeted irradiation of the areas to undergo therapy,in particular in the oral cavity, is facilitated. Furthermore, theapplicators are preferably embodied at least partially flexible so thatundesired injuries are avoided.

In one preferred embodiment, the light conductor has a defined geometryof the light exit area such that the light exit is matched to the shapeof the sites to be irradiated in the area to undergo therapy, wherebyeither a two-dimensional or physical three-dimensional radiation area isproduced. Furthermore, the applicator and/or the light conductor has atits tip a spacer with which an active circle of the exiting light isindicated and/or the correct or prescribed irradiation distance isestablished. In accordance with another embodiment, the light conductorgeometry is such that penetration into narrow cavities and/or pockets oftissue with complex shapes is enabled and/or these can be opened gently.Advantageously, the light conductor has a conical tip, specificallyusefully with an angle of 1.5 to 4° to the perpendicular. In addition,it has proved particularly advantageous to provide the light conductorin the area of its tip with a light exit surface having a prescribedmicrostructure ranging from 10 μm to 200 μm. The tip of the lightconductor preferably has a micro-roughness with an Ra value ranging from10 to 40 μm, preferably 20 to 30 μm. Moreover, the connector body of theapplicator is embodied as a plug-in and/or screw-in connector with anintegrated stop, thus ensuring defined positioning in the axialdirection of the light conductor inserted into the radiation device withrespect to the light source.

For the inventive use of the arrangement, the light-activatablesubstance that preferably contains stain is first applied in a highconcentration to the area to undergo therapy and then rinsing isperformed with a medium, in particular water and/or with the mostalkaline possible pH. Thereafter, the irradiation by means of the lightfrom the radiation device is performed, whereby in a preferred manneroptimized cell damage occurs. It has proved particularly effective tofirst apply the light-activatable substance in a high concentration tothe area to undergo therapy and subsequently to rinse with a medium, inparticular water, and/or with oxygen partial pressure as high aspossible, and finally to perform the irradiation by means of the lightfrom the aforesaid light source, whereby optimized cell damagepreferably occurs. Furthermore, it has proved particularly useful thatafter the light-activatable substance is applied in a high concentrationto the area to undergo therapy and furthermore prior to the irradiationby means of the light from the light source, the quantity oflight-active substance is reduced, specifically in particular by wipingand/or dabbing and/or suctioning and/or blowing air.

The structure of the arrangement and its inventive use are described indetail in the following. The arrangement contains:

1. Light-Activatable Substance:

The light-activatable substance present in solution, for instancemethylene blue, which preferably contains a stain and is called aphotosensitizer, is preferably added to a syringe and sterilized andready for use. In particular a 26-g cannula is provided for theapplication to the area to undergo therapy, and it has in particular anexterior diameter of 0.45 mm, a length of 25 to 40 mm, and in particularis embodied angled at 35 to 40 degrees and elastic.

2. Radiation Device with Light Source, in Particular Laser Device orTherapeutic Laser, Preferably in the Following Embodiments:

a. With optical system, in particular lens packet, and preferably with athreaded connector to the light conductor coupling.

b. With direct beam coupling without lens packet, with clear space infront of the diode so that without attached light conductor only alittle light escapes diffuse from the access provided for coupling thelight conductor. The arrangement is furthermore preferably such thatwhen using a diode with monitoring the back-scattered light regulatesthe diode.

The radiation device preferably contains a blocking device, by means ofwhich light is prevented from exiting as long as an applicator is notconnected to the radiation device.

3. Application System

Single-use optics or applicators that in particular are each used onlyonce and preferably have a light conductor and plastic covering. Theseare preferably flexible and/or sterilized and/or ready to use and/orcompatible with both of the aforesaid radiation devices. Glass orplastic is provided as the material for the light conductor(s) inparticular with a numerical aperture preferably greater than 0.5 μm inorder to couple as much light as possible and furthermore to emit thelight in a large area. Due to the detachable connection between theradiation device and the applicators, it is particularly important thatthe applicator in the framework of the invention is used only once andthereafter is disposed of as a comparatively simply constructed andcost-effective component and as a “disposable product”.

Two embodiments of the applicators are usefully provided:

a. Pocket probe with conical emitting area in particular for irradiatingthe periodontal pocket. In one step the pocket is opened, tissue ispushed to one side, and the area is irradiated with radiation to thefront and in a circle. The surface is roughened so that the radiation ofthe light is diffuse (for instance sanded with sandpaper 100).

b. Surface probe, preferably with spacer for irradiating superficialsites,

i. the length of which marks the correct distance to the tissue,

ii. the angle of which marks the area in which the therapeuticallyrequired light output is to be applied, whereby overlapping irradiationof an area is reduced.

4. Furthermore, in one preferred further development a therapycontroller and/or a program for the PC and/or an independent display andcontrol unit. These provide control and orientation for the operatorduring the therapy. This permits above all selection of the size of thesurface to be irradiated or the number of teeth and in particulardisplays:

a. the time the photosensitizer takes effect,

b. the time for rinsing the site,

c. the time for irradiating each cm2 or tooth with an acoustic signalfor the end of the irradiation for each tooth or cm²,

d. the end of the treatment.

The components of the arrangement are explained in the following:

The energy source or light source of the radiation device is embodiedsuch that there is sufficiently high penetration of the light in thetissue in the relevant wavelength range since long-wave radiationpenetrates deeper into the tissue than short-wave radiation.Sufficiently deep penetration into the tissue with light occurs in thearea of the absorption maximum of the light-activatable substance, forinstance methylene blue (664 nm in NaCl or 655 nm in 96% ethanol). Inthe so-called optical window between 600-900 nm, the light is veryslightly absorbed by chromophores such as hemoglobin or melanin.

Above all laser systems are suitable as energy or light sources. Thelaser (light amplification by stimulated emission of radiation) is alight source that can emit monochromatic, coherent, and collimated lightat a high power. Coherent light includes temporal and spatial coherencein the wave trains.

Essentially photochemical processes are effective in the range of theinventively provided low-power and low energy densities (0.1-100mW/cm2). In these cases, the absorption of light does not primarily leadto the tissue heating up. These effects produced in biological materialsusing athermal laser applications are called “laser-inducedbiostimulation”. Such lasers are used as the light source for thephotodynamic therapy (PDT) using the photosensitizer. Photothermallyinduced effects can also occur with these lasers when using higher powerdensity or higher energy density.

In diode lasers, semiconductor crystals are used as the active mediumand when excited emit coherent radiation in the VIS or IR range. Inthese lasers, photons are produced directly using electrical current.

In connection with the photosensitizer that is preferably used, aspecial diode laser is used for the radiation device, hereinafterreferred to as the HELBO TheraLite. The HELBO TheraLite diode laser issuitable in particular for methylene blue.

This laser system is characterized by the following properties:

Light source Diode Wavelength 660 nm (+5) Power Max. 100 mW Mode Cw orcontinuous Light output power >40 mW < 50 mW Cooling system Air Energysupply Battery or accumulator

The application system inventively enables the transmission of the lightor laser radiation. The application system provides the desired beamgeometry at the site of application and enables simple handling of thelaser radiation for therapy. The optical fiber is part of theapplication system.

One of the goals of effective and controllable therapy in the oralcavity is attaining the most homogeneous possible irradiation of thesurface of the oral mucosa. However, the oral cavity is characterized bycomplex geometry and by the presence of very differently absorbingstructures such as bones, teeth, and mucosa that clearly deviate fromplane geometry. This is assured with the inventive applicators.

Optical fiber systems can conduct the required energy even into sitesthat are difficult to access such as in the oral cavity. For couplinginto an optical fiber, the primary beam from the laser in the radiationdevice is focused on the fiber end either directly or through a lenspacket. The numerical aperture of the fiber determines the couplingangle such that the radiation largely enters the light conductor.

The beam divergence of the optical fiber is also determined by the typeof coupling into the fiber head and of the radiation device also by thenumerical aperture (sine of the aperture angle) of the fiber itself. Ahigher divergence enables a wider transmission angle.

When fibers having a steep drop in energy, or having widely fluctuatinglight distribution over the irradiated surface, are used, theirradiation field is frequently irradiated in an overlapping manner.

In comparison to the bare fiber, the preferably provided microlens fiberhas the most homogeneous irradiation profile. With an optimizedmicrolens fiber, a power distribution with homogeneity of approximately96% can be obtained over the entire irradiated surface. Overlapping theirradiation fields is not necessary when using a microlens fiber, sothat it is possible to cover the infected area in a highly efficientmanner and there are no unnecessary areas of overlap.

The application mode (extraoral or intraoral) is a function of the focussize, which is selected according to the findings.

One preferred alternative is provided by inventive fibers with a veryhigh a numerical aperture with which uniformly irradiated sites can alsobe produced.

A numerical aperture of at least 0.5, preferably 0.7 or higher, isinventively provided in order to avoid complex grinding of fiber tipsand to be able to maintain a clinically reasonable distance of 0.5 to 1cm for the irradiation of intraoral areas.

In particular the following application system with the applicators,which are embodied as a pocket probe and/or a surface probe, is used inthe framework of the invention. These applicators contain plastic lightconductors that are embedded in a covering, a coupling surface with aconnector to the radiation device, in particular a laser device, and aspecifically ground radiation area and/or a radiation area having amicrostructure.

The invention is described in greater detail in the following using thespecial exemplary embodiments depicted in the drawings without thisresulting in a restriction.

BRIEF DESCRIPTION OF THE DRAWINGS

Accompanying the specification are figures which assist in illustratingthe embodiments of the invention, in which:

FIG. 1 contains a table of measurement results for a pocket probe thatwas arranged perpendicular to a glass surface at an output power of 15.5mW;

FIGS. 2 and 3 depict a pocket probe and a spot probe for applicators;

FIGS. 4 and 5 depict the structure and assembly of the applicationsyringe 14 that contains the light-activatable substance in solution;

FIG. 6 depicts the light conductor piece of the applicator, not yet bentand without the connector body, which is arranged in the area 16;

FIG. 7 depicts the light conductor piece for the pocket probe, the freeend 22 being free of the protective jacket 4 and having a length of 7mm;

FIG. 8 depicts an applicator similar to FIG. 4, a spacer 20 beingarranged on the free end;

FIG. 9 depicts a bent light conductor piece of a pocket probe similar tothat in FIG. 3, the free light conductor end 8 projecting from theconnector body 6 at a predetermined length, in this case 10 mm;

FIG. 10 depicts side elevations of one preferred embodiment of thespacer 20;

FIG. 11 depicts elevations of the surface probe with inwardly contractedlight conductor with the spacer 20;

FIGS. 12 and 13 provide partial depictions of surface probes, whereby inaccordance with FIG. 12 the surface probe has a numerical aperture of0.72;

FIGS. 14, 15 and 16 depict the optical system of the radiation device,whereby in accordance with FIG. 14 a perpendicular beam divergence angleof no more than 35° is provided and in accordance with FIG. 15 aparallel beam divergence angle of no more than 10° is provided;

FIG. 17 illustrates the radiation device without the optical system,whereby a battery tube 44 for the batteries required for supplyingcurrent to the electronics is present in a housing tube 42;

FIG. 18 depicts one particular embodiment of the invention andillustrates the radiation or laser device from the side, withoutapplicator;

FIG. 19 depicts the embodiment of FIG. 18 and illustrates two exemplaryembodiments of applicators, whereby the applicator A illustrated at thetop is a pocket probe similar to that in FIG. 2, while applicator B,illustrated therebelow, is a surface probe similar to that in FIG. 3;

FIG. 20 depicts the embodiment of FIG. 18 and illustrates a lockingmechanism containing a rotationally symmetrical locking body 58 that hasan “H”-shaped cross-section and that in its center has a hole 60 with adiameter that is 1.01+0.02 mm;

FIG. 21 depicts the embodiment of FIG. 18 and provides the explodedillustration of the locking body 58;

FIG. 22 depicts the embodiment of FIG. 18 and illustrates the lockingdisk 62 in FIG. 22;

FIG. 23 depicts the embodiment of FIG. 18 and illustrates a sectionthrough the radiation device;

FIG. 24 is an enlargement of the anterior part of the device in FIG. 23;

FIG. 25 depicts the embodiment of FIG. 18 and illustrates a section inan axial plane through the locking body 58, whereby it is easy to seethe H-shaped sectional surface;

FIG. 26 depicts the embodiment of FIG. 18 and illustrates a section inan axial plane through the locking disk 62 that contains the hole 106,already described, in the center; and.

FIG. 27 depicts the embodiment of FIG. 18 and illustrates the lockingspring 64.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 contains a table of measurement results for a pocket probe thatwas arranged perpendicular to a glass surface at an output power of 15.5mW. The measured powers are provided in mW depending on the diameter ofan optical fiber and the distance from the light source. It should bestated at this point that a photosensitizer with a high concentration ispreferably used, specifically preferably greater than 0.1%, inparticular on the order of magnitude of 1%, in a solvent, whereby inaccordance with FIG. 1 methylene blue in solution is provided for thephotosensitizer.

FIGS. 2 and 3 depict a pocket probe and a spot probe for applicators. Itis understood that the dimensions provided in millimeters as exampleshere and in the other figures can be modified where needed. Theapplicators contain a light conductor 2 embodied as a fiber that is forthe most part exteriorly surrounded by a protective jacket 4. Theapplicators furthermore have a connector body 6 that is preferablyembodied as a Luer plug and that connects or is received in the head ofthe radiation device. The light conductor 2 passes through the connectorbody 6 and its end 8 projects beyond by a predetermined length,specifically by 5 mm in accordance with FIG. 2. The light conductor end8 is not provided with a protective jacket and when the applicator isconnected is inserted into the head part of the radiation device andpositioned therein. The light conductor 2 is embodied at least partiallyflexible and/or contains a curved area 10. The dimensions of theapplicators are provided such that they can be inserted into the oralcavity with no problem.

In the laser used in both applicators, the laser radiation exits in acircle with a 1-mm core diameter due to the material properties and thegrinding geometry in the area of the tip 12 at an initial divergenceangle ranging from 30 to 60°, preferably 40 to 55 degrees, frontally orin particular for the pocket probe ranging from 220 to 300 degrees,preferably 240 to 290°, in particular 260 to 280 degrees.

These properties render the applicators easy-to-use optical tools forprecise irradiation of surfaces that have simple shapes, but alsosurfaces that have complex shapes.

The structure and assembly of the application syringe 14 that containsthe light-activatable substance in solution are depicted in FIGS. 4 and5. The syringe 14 that contains the light-activatable substance insolution is supplied ready-to-use. Prior to use, the cap must becarefully rotated to remove it from the tip and the enclosed sterilecannula must be fixed on the Luer lock adapter of the syringe. Careshould be taken that the fingers are correctly positioned. Carefullyexplain the procedure to the patient prior to treatment. Once the areato undergo therapy has been prepared properly in terms ofclinical-surgical aspects, open the package; one blister-packet with thelight-activatable substance, one blister-packet with a cannula, and anyprinted material are removed. Read the printed material prior to firstuse. Maintaining sterile conditions, empty both blister-packages overthe sterile surgical tray. Syringe and cannula are thus sterile andready for use in the sterile area. Carefully remove the silicon stopperfrom the syringe and fix the cannula by rotating on the Luer cone.

FIG. 6 depicts the light conductor piece of the applicator, not yet bentand without the connector body, which is arranged in the area 16. Theprotective jacket 4 is provided between this area 16 and the free end18. Furthermore, arranged at the free end 18 is a spacer 20 by means ofwhich a defined distance is maintained from the area to undergo therapy,in this case 5.5 mm.

FIG. 7 depicts the light conductor piece for the pocket probe, the freeend 22 being free of the protective jacket 4 and having a length of 7mm. The free end 22 is ground and has a surface with a 100 grain size,corresponding to processing with abrasive paper. The tip 24 of the freeend 22 is embodied stub-like and/or is provided with a radius. Thesurface preferably has a predetermined micro-roughness. It preferablyhas an Ra value ranging between 10 and 40 μm, preferably ranging between20 and 30 μm.

FIG. 8 depicts an applicator similar to FIG. 4, a spacer 20 beingarranged on the free end. In this embodiment, the light conductor end 8projects from the connector body 6, specifically at a length of 10 mm.

FIG. 9 depicts a bent light conductor piece of a pocket probe similar tothat in FIG. 3, the free light conductor end 8 projecting from theconnector body 6 at a predetermined length, in this case 10 mm.

FIG. 10 depicts side elevations of one preferred embodiment of thespacer 20.

FIG. 11 depicts elevations of the surface probe with inwardly contractedlight conductor with the spacer 20.

FIGS. 12 and 13 provide partial depictions of surface probes, whereby inaccordance with FIG. 12 the surface probe has a numerical aperture of0.72.

FIGS. 14 through 16 depict the optical system of the radiation device,whereby in accordance with FIG. 14 a perpendicular beam divergence angleof no more than 35° is provided and in accordance with FIG. 15 aparallel beam divergence angle of no more than 10° is provided. As canbe seen in particular from the exploded illustration in accordance withFIG. 16, the laser diode 26 is arranged in a threaded sleeve 28. This isa multimode laser diode with 100 mW continuous for 670 nm including amonitor diode. There is an objective lens 32 in the tapered part 30, alens holder 34 being provided for an additional objective lens 36.Furthermore provided are an adjusting ring 38 and a receiving body 40.

FIG. 17 illustrates the radiation device without the optical system,whereby a battery tube 44 for the batteries required for supplyingcurrent to the electronics is present in a housing tube 42. A cap 46 isdetachably connected or can be detachably connected to the housing tube42 via a threaded connector at the posterior end, the lower end inaccordance with the drawing, of the housing tube 42. Furthermore, akey-operated switch 48 is provided at the posterior end of the housingtube 42 or the cap 46 by means of which the irradiation or laser devicecan be turned on and off. Arranged at the anterior end of the housingtube, which is embodied as a protective housing, is a head part 50 thatis embodied for receiving the applicators and for decoupling the lightbeam using the central bore 52.

The following light output is available for irradiation using thepreferred embodiment of the radiation device, which is also called theHELBOTherLite laser:

Pocket probe Spot probe Irradiation Radial, 250-280 degree range, 40-60degree range, in in particular largely 270 particular largely 50 degreesfrontally degrees frontally Power density >40 mW/cm² >40 mW/cm²

The preferably used light-activatable substance is a sterile, isotonic,deep blue odorless aqueous liquid. It contains phenothiazin-5-ium,3,7-bis(dimethylamino)-chloride for coloring and sensitizingmicroorganisms for the lethal photodynamic therapy using the radiationdevice.

1 mL of the solution contains:

1% phenonthiazin-5-ium, 3,7-bis (dimethylamino)-, chloride

Glucose for isotonization

MHPC (methylhydroxypropylcellulose) for adjusting the viscosity

Citrate for buffering the solution

The osmolarity is approximately equal to that of human tissue.

The in solution with the light-activatable substance is packed in aglass syringe and sealed with a stopper made of silicon. The fillquantity is 0.5 mL+/−0.1 mL. The glass syringe is sealed with a blisterand is steam-sterilized in a validated sterilization process. Theaforesaid solution is usefully packaged in five blister-packs with oneprinted insert in a box. Five 28 G cannulas that are each also packed ina blister-pack and sterilized are also enclosed.

During the lethal photodynamic laser therapy, the light-activatablesubstance stains and sensitizes microorganisms in local superficialinfections, in particular in the mouth, jaw, and facial areas.Subsequent irradiation with the radiation device eliminates stainedmicroorganisms and restores the natural oral bacteria.

Topical application occurs in the area of the infection without or witha surgical incision and curettage and paralesional as follows: thepatient rinses with water twice for 20 seconds. Saliva or blood adheringto the surfaces to be treated is suctioned or dabbed off in order toprevent dilution of the photoactive substance.

The light-activatable substance is slowly applied by means of thesyringe, covering the surface of the infected tissue. The quantity mustbe selected such that the light-activatable substance moistens thesurface of the infected areas in a layer that is as thin as possible.Make sure that the folds and pockets in the tissue are completelymoistened. Where required, when the morphology is complex, carefullydistribute with the air syringe. The light-activatable substance needsat least 60 sec to take effect. After rinsing for at least 3 sec whilesuctioning excess solution (deposits of stain must be removed!),irradiate with the radiation device. The correct dosage of energysupply, the irradiation, is essential for the germ-reducing effect andthus for treatment results.

The operator controls the therapy using treatment time for a givensurface area treated as the critical variable for determining therequired energy density (J/cm²). For each cm² or tooth there should beat least 1 minute of irradiation time with the radiation device.

The following formulas are used for calculating the irradiated surface Aof a lesion with a radius r during the irradiation:

a: with pocket probe: surface of defect F=Width W*Height*2 and thus perquadrant:

Teeth 1 2 3 4 5 6 7 8 Width, cm 0.6 1.2 1.8 2.4 3 3.6 4.2 4.8 Height, cm0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 3D factor 2 2 2 2 2 2 2 2 Surface area,cm² 0.96 1.92 2.88 3.84 4.8 5.76 6.72 7.68 Power, mW 50 50 50 50 50 5050 50 Surface density, W/cm² 0.052 0.052 0.052 0.052 0.052 0.052 0.0520.052 Irradiation, sec 60 120 180 240 300 360 420 480 Energy density,J/cm² 3.125 3.125 3.13 3.125 3.125 3.125 3.125 3.125

Irradiation Protocol for the Pocket Probe

B: with the spot probe: Surface of defect F=(πr2)

The power density (FD) is calculated as follows:

FD (Watt/cm²)=power (Watt)/irradiated surface (cm²)

The energy density (ED) is calculated as follows:

ED (Wattsec/cm²)=power (Watt)*time sec/irradiated surface (cm²)

The dosimetry selected is consolidated in the following table. As arule, irradiation is performed at a distance of 0.55 cm and at a powerdensity of 0.051 W/cm² a total dose of 3 J/cm² is used.

Irradiation unit 1 1 1 2 3 4 5 6 Diameter, cm 1.8 0.9 1 1 1 1 1 1Radius, cm 0.9 0.45 0.5 0.5 0.5 0.5 0.5 0.5 Distance, cm 1 0.5 0.55 0.550.55 0.55 0.55 0.55 Surface area, cm² 2.5434 0.6359 0.79 1.57 2.355 3.143.925 4.71 Power, mW 40 40 40 40 40 40 40 40 Surface density, W/cm²0.016 0.063 0.051 0.051 0.051 0.051 0.051 0.051 Irradiation, sec 60 6060 120 180 240 300 360 Energy density, J/cm² 0.94 3.77 3.06 3.06 3.063.06 3.06 3.06

Irradiation Protocol for Spot Probe

An effective phototoxical effect can be induced if bacteria are stainedusing light-activatable substances or vital stains such as MB andirradiated with light of a suitable wavelength. Unstained cells do notdemonstrate any toxic damage. Photochemical killing of possiblepathogenic bacteria is performed at fur farms and zoos in that methyleneblue is added to the drinking water.

MB has been used for 25 years as a photosensitizer for local treatmentof herpes-induced illnesses. The dark toxicity and phototoxicity (PDT)of intratumorally applied methylene blue was explored in experiments oncolon tumors. These tumors were not destroyed by irradiation alone witha low total dose (6 J/cm²) or by administering the substance (20 μg/mL)alone.

Adding MB can lead to systemic secondary effects such as increasedperspiration, nausea, and vomiting.

Oral administration can lead to gastrointestinal complaints and todysuria. The ingredients for preparing the solution are:

Active/inactive ingredients 1 mL contains Methylene blue x H2O 10.00Trisodium citrate x 2 H2O 0.433 Citric acid x 1H2O 1.667 MHPC 10.00Sodium chloride 9.00 Water for injection 1000

Ingredients of Light-Activatable Substance:

Using the present biocompatibility assessment, the substances used inthe preparation are evaluated with respect to their biocompatibility,teratogenity, and mutagenity under the given application conditions asacceptable in terms of the desired treatment goal.

Using topical application of the photosensitizer (PS), there are none ofthe significant problems associated with systemic use of a medicationsuch as antibiotics, nor of systemically used PS, such as e.g. substancetoxicity and generalized multi-week photosensitization of the skin.Topical application increases specificity so that healthy tissue, e.g.mucosa in the area surrounding the lesion, is protected.

The treatment can be repeated due to the minor nature of the secondaryeffects. The therapy is furthermore distinguished by its non-invasivenature.

The local concentration is also influenced in that as a rule increasedsalivation is induced in the oral mucosa after local application of thePS. This leads to a decrease in the PC concentration and reduces thestain's penetration into the lesion. Moreover, saliva proteins candeactivate the PS because of non-specific binding. Introducing the PS ina solution, in particular a viscous solution, inventively reduces themixing, dilution, and reaction with saliva for the treatment period.

After the period for taking effect, which is at least 60 sec, inaccordance with the invention the excess PS is removed in order toincrease the light transparency of the treated tissue.

Measurements demonstrate that a 100-μm liquid film of the solution withthe light-activating substance that stands on the tissue reduces theeffective energy density by 97%. In accordance with the Beer-LambertLaw, the light is further weakened when the layer thickness is doubled.Thus therapeutically effective irradiation is not possible with thelight-activating substance when there is excess solution.

An energy density of 50-100 J/cm² is recommended for effectivelyapplying PDT to oral mucosa lesions. The energy dose should be matchedto the type and localization of findings. Since the oral mucosa aregenerally very sensitive to pain, power densities greater than 150mW/cm² should be avoided. Power densities between 200 and 500 mW/cm² canlead to non-specific thermal tissue damage.

The surface area irradiated should be selected to be larger than thesurface area of the lesion in order to attain a uniform dose in the areaof the lesion.

The light dose of approximately 100 J/cm² for the PDT can be attained indifferent manners: high power density and short exposure times or lowpower density and long exposure times. Due to the aforesaid thermaldamage, high powers are not used. On the other hand, it is not possibleto obtain a photodynamic effect when the power densities are too low,even if the irradiation periods are correspondingly long.

Methylene blue solutions are able to reduce the number of all examinedmicroorganisms in the culture medium being used.

Methylene blue solutions reduce almost all Gram positive bacteria in aconcentration of 25-44 μmol in vitro.

Completely reducing Gram negative germs requires 3-30 times higherconcentrations. P. aeruginosa was reduced from 100 mW/cm² by 3.5 log₁₀CFU at a concentration of 200 ˜mol and an energy density of 100 mW/cm².

The observed dark toxicity was higher for toluidine blue (TB) than formethylene blue (MB). This is consistent with the distributioncoefficient P that was determined to be 0.33 for TB and 0.11 for MB.

Since log P was <0, both stains can be characterized as hydrophilic and,at least theoretically, should be able to fit the water-filled porinprotein channels of Gram negative bacteria.

While dark toxicity for Gram positive bacteria was nearly unrelated totype, the dark toxicity for Gram negative bacteria is quite clearly afunction of type and specifically corresponds to the trans-membranepermeability coefficient of the exterior membrane of Gram negativebacteria.

Dark toxicity was a function of both the concentration and theincubation period prior to irradiation.

S. aureus was identified as the most resistant bacterium for the Grampositive group, and it required the highest concentrations for itsdestruction.

P. aeruginosa was identified as the most resistant bacterium for theGram negative group, and it required the highest concentrations for itsdestruction.

In the case of Gram negative bacteria, photodynamic sensitivity is afunction of trans-membrane permeability, and hydrophilicity, positivecharge, and low molecular weight of the stain molecule promote efficacy.

For the present therapy, only 60-sec periods for taking effect withsubsequent rinsing prior to irradiation are provided for the treatmentof microbially infected areas.

The selected parameters of therapy, in particular:

1% concentration of the light-activating substance in solution

Energy of 2.4 J

Power density of 50 mW/cm²

And energy density of 3 J/cm²

Incubation time of 60 sec with subsequent rinsing of solution aresuitable for assuring a positive treatment result. On the other hand,possible risks and secondary effects are limited when these conditionsare observed and, when properly explained, seem to be acceptable inlight of the expected positive aspects for patients.

PDT is based on a photochemical process in which the photosensitizers(PS) are activated by means of laser radiation and the radiated energy“portions” such that it is available for forming locally toxicallyacting oxygen radicals. Thermal damage to the tissue can be preventedwith certainty at the selected energy and power densities of 3 J/cm² and50 mW/cm², respectively.

The clinical application of PDT is possible since the stain solutionsselectively color cell systems, while the interaction with theepithelium is very limited. Studies of normal oral mucosa indicated thatthe penetration depth of MB solutions after 10-min incubation time waslimited to just the first 1-2 exterior layers of cells of theepithelium. Furthermore, the life expectancy of the active radicals andtheir precursors is microseconds, so that it is practically assured thatthere are no concomitant destructive effects in healthy tissue due todiffusion, since there is not enough time for this.

The effect is thus linked to the presence of the stain molecule in thePS.

The selection of for instance methylene blue for the photodynamic activesubstance in the preparation is based, first, on the low toxicity ofmethylene blue under the selected conditions, and second, on thefavorable absorption maximum at 664 nm:

Capable and efficient diodes for producing the laser beam are availablefor this wavelength

Treatment is performed in the visible light spectrum, which is crucialfor the therapy's safety and efficiency

The depth the light penetrates into the tissue in this wavelength rangeis adequate for also being able to reach penetrating bacterial colonies

The singulet oxygen formation is the critical mechanism for killing thegerms, while healthy cells cause these radicals to deteriorate due tocatalases

Can, on the other hand also be some protection due to the efficacy ofvitamins like vitamin C and E.

Given the results of the spectro-photometric tests of MB with andwithout irradiation, there was a nearly linear decrease in extinction asapplied energy density increased. Photo-bleaching with destruction ofthe stain molecules occurs to a significant extent at energy densitiesthat are greater than the therapeutically applied energy density by afactor of 7.

A photo-biological effect occurs in this area that promotes tissueregeneration and stabilizes local metabolism

Methylene blue is available in a pure and documented form the use in apreparation leads to stable solutions

These solutions are simple and safe to handle under conditions prevalentin medical surroundings when used with appropriate caution

The waste that occurs during use is relatively harmless

Coordinating stain and light source provides a therapeutically effectivesystem that demonstrates effectiveness against Gram positive and Gramnegative bacteria as well as against fungus such as candida albicans andthat, by reducing the number of microorganisms, supports the body's owndefense for a short period in order to improve clinical symptoms.

Using the HELBO PocketProbe applicators, it is possible to inventivelyapply an energy density largely ranging from 1 to 7 J/cm², preferablyfrom 2 to 4 J/m2, in particular a largely uniform energy density of 3J/cm², even in complex sites around and between teeth in the posteriorareas of the oral cavity.

By using the photo-dynamic therapy, it was possible to observe rapidfreedom from pain and accelerated wound healing due to supportingphoto-biological effects.

The only secondary effects observed during the therapy were occasionalburns; these healed rapidly after the treatment concluded, however.

One particular embodiment of the invention is described in greaterdetail in the following using FIGS. 18 through 27. The radiation device,which is also called the therapy laser hereinafter, is for photo-dynamictherapy (PDT) and is in particular embodied as a laser device. Itcontains a blocking device by means of which the light path isautomatically uncovered when an applicator that contains a lightconductor is attached. As long as the applicator and/or the lightconductor is not attached to the radiation device/laser device, theinventively embodied blocking device prevents laser light from exitingfrom the laser device. The blocking device in particular contains alocking body that is embodied and arranged such that laser light cannotexit unless the applicator or light conductor is attached. The lockingbody of the blocking device is arranged in a changeable position, and itcannot be moved from this position for uncovering the light path unlessthe applicator or light conductor is properly attached. The blockingdevice is in particular integrated in the head part of the radiationdevice. Alternatively, the blocking device can be at another location onthe radiation device and/or embodied differently, and in particular canbe integrated into the optical system. The inventive radiation deviceassures that the light is coupled directly from the diode or laser diodeinto the light conductor such that

1. low losses occur because an optical fiber with a high numericalaperture is used, in particular greater than 0.5, preferably greaterthan 0.7, which ensures that a relatively large surface area isuniformly irradiated because the light beam opens up when it exits thefiber,

2. because of the installed blocking device, the light cannot exitunless the light conductor is inserted or attached, and otherwise thelight cannot exit directly out of the laser device. Thus the laserdevice can be operated without protective goggles and without having todesignate a Laser Protection Representative, as would fundamentally benecessary at the provided laser device output.

Due to the high numerical aperture of the light conductor used, theaforesaid scatter effect is attained when the light exits/when the areato undergo therapy is irradiated and on the side of the applicator orlight conductor facing the laser device there is a collective effectsuch that a lens system between the laser or diode and the lightconductor is not necessary.

When using the radiation or laser device and/or when using thearrangement for photo-dynamic therapy, the following listed steps areparticularly important:

1. First apply the solution with the photosensitizer in a highconcentration to the area to undergo therapy so that the solutionpenetrates as rapidly as possible, especially into the plaque on teeth.

2. In addition, it is preferred that there be rinsing with a medium, inparticular water, with an ion concentration that is as low as possibleso that bacteria and/or cell membranes are weakened due to the osmoticpressure gradients thus produced. It should be stated that for instancea physiological table salt solution would not work well due to therelatively high ion concentration. The pH of the medium is preferablyalkaline. The pH is preferably 7 to 9. The oxygen partial pressure ispreferably high. In the framework of the invention, the medium, inparticular prepared tap water, has an oxygen partial pressure rangingfrom 4 to 6 mg/L for rinsing. The medium is usefully enriched withmolecular oxygen up to 14 mg/mL. Furthermore, peroxide enrichment hasproved useful in accordance with the invention, specifically as 0.5% to3% hydrogen peroxide solution.

3. Due to the prior rinsing with a medium of low concentration, optimumcell damage occurs during the irradiation by means of the laser light.

Description of the Irradiation Device or Laser Device

The device is operated with batteries or accumulators and for the lightor beam source uses a semiconductor laser (laser diode) that is operatedcontinuously (cw). FIG. 18 illustrates the radiation or laser devicefrom the side, without applicator. The beam source is built into acylindrical protective metal housing 42. The length of the protectivehousing containing the housing tube 42 is about 124 mm, the diameter isabout 16 mm. After the batteries or accumulators have been inserted, acontact cap 46 is screwed onto the end of the protective housing 42where the batteries are to be inserted. Placing the key-operated switch48 formed as the closure cap into the contact cap 46 renders the unitready to operate. The operating mode is indicated by differently coloredLEDs 54.

The head part 50 is screwed onto the protective housing 42 at the otherend of the protective housing 42 and glued thereto so that direct accessto the beam source is prevented. The head part 50 receives theapplicators and is thus for coupling the laser beam, and it alsocontains the locking mechanism. Pressing a button 56 activates thesemiconductor laser.

Applicators

FIG. 19 depicts two exemplary embodiments of applicators, whereby theapplicator A illustrated at the top is a pocket probe similar to that inFIG. 2, while applicator B, illustrated therebelow, is a surface probesimilar to that in FIG. 3. Both applicators comprise a transparentplastic light conductor with a diameter of about 1 mm, have a Luer plugfor being received on the head of the laser device, are bent, and aresurrounded with a white protective jacket between Luer plug and beamexit end. The light conductor end (without protective jacket) in theLuer plug is inserted into the head of the protective housing.

Applicator A has a slightly conical tip, the surface of which isroughened on the last 5 mm. The rough surface ensures that the laserlight is emitted in nearly all spatial directions, the most energy beingemitted in the axial direction of the light conductor. Applicator B hasa flat end face as the exit surface for the laser light. In addition, awire loop is built-in on the light conductor end as a spacer. Incontrast to applicator A, the laser light has diverging, conicalradiation characteristics, which means more energy is emitted in theaxial direction. Therefore applicator B was used for all othermeasurements, since it contains the greater potential for risk from thestandpoint of laser safety.

Blocking Device/Locking Mechanism

The locking mechanism depicted in FIG. 20 contains a rotationallysymmetrical locking body 58 that has an “H”-shaped cross-section andthat in its center has a hole 60 with a diameter that is 1.01+0.02 mm.The laser diode is positioned in the recess of the “h” that faces awayfrom the beam exit and in the activated condition emits light throughthe hole 60 in the locking body 58 in the direction of the beam exit.

Located in the depression of the “H” that faces the beam exit is a roundlocking disk 62 that also has in its center a hole with a diameter thatis 1.01+0.02 mm. The exterior diameter of this disk 62 is substantiallysmaller than the interior diameter of the locking body 58, so that inaccordance with FIG. 20 the disk can be placed in the depression. Thelocking disk is held eccentricially by means of a wire spring (lockingspring), however. Thus this disk 62 covers the hole in the locking bodyand the laser light cannot exit. The wire spring 64 is conducted in agroove on the circumference of the locking disk. As can be seen fromFIG. 21 and the exploded illustration of the locking body 58 and thelocking disk 62 in FIG. 22, the locking body 58, in whose recess thelocking disk is movably arranged, is arranged in a diode holder 68. Inthe exploded depiction in FIG. 22, it is easy to see the two aforesaidholes of the locking body 58 and locking disk 62.

It is not until the light conductor of the applicator is inserted up tothe stop that the locking disk 62 is pressed into the central positionso that the hole of the locking disk 62 and the hole of the locking body58 coincide and the laser light can be coupled into the light conductor.If the light conductor is withdrawn, then the wire spring 64 presses thelocking disk 62 back into the starting position and the laser light isblocked. In the framework of the invention, other restoring elements canalso be provided instead of the wire spring 64 depicted here in order tomake it possible for the laser light to exit only when the applicatorand in particular its light conductor end are properly connected to theradiation device.

FIG. 23 depicts a section through the radiation device and FIG. 24 is anenlargement of its anterior part. This radiation device fundamentallycorresponds to that explained in the foregoing and additionally containsthe blocking device/locking mechanism. Arranged in the battery tube 44that is enclosed by the housing tube 42 are three batteries 70 that areactuated by means of a battery spring 72. A socket 74 is arranged in aguide 76, whereby furthermore present are a disk 78 and a spacing disk80. Furthermore, two pins 82, 83 are provided for contacting withelectronics or an electronic bar 84. The button 56 that can be actuatedfrom outside is arranged on the electronics bar 84, whereby inparticular for sealing of a key film 86 together with a ball 88 areprovided. An area with a hammer 92 is provided in the anterior directionadjacent to the interior area with the electronics 84 and separated bymeans of a rear insulation 90, whereby an anterior insulation is alsopresent. Two O-rings 96, 97 are furthermore arranged inside the housingtube 42. Arranged at the anterior end of the housing tube 42 is the headpart 50, the anterior end of which engages in the connector body or Luerplug 4 of the applicator (not shown here). The diode holder 68, alreadyexplained in the foregoing, with the laser diode 26 is arranged in thehead part 50, whereby an insulating disk 98 and a printed board 100 forthe diode, including wires necessary for contacting, are provided to therear toward the battery tube 44. In addition, provided in the directionof radiation in front of the laser diode is a protective film 102 bymeans of which in a preferred manner the laser diode can be protectedagainst exterior influences, an O-ring 104 also being provided.Moreover, the locking disk 62 and the locking spring 64 are arranged inthe interior recess of the head part 50 of the locking body 58, alreadyexplained.

FIG. 25 depicts a section in an axial plane through the locking body 58,whereby it is easy to see the H-shaped sectional surface. It isunderstood that the dimensions given for the special embodiment inmillimeters can also be different.

FIG. 26 depicts a section in an axial plane through the locking disk 62that contains the hole 106, already described, in the center. On itsexterior circumference the locking disk has a groove 108 in which thewire or locking spring engages.

Finally, FIG. 27 is a depiction of the locking spring 64. It does nothave to be particularly stressed that the dimensions of the lockingspring and the other components can also be different for otherembodiments.

Functional description—blocking device

The blocking device contains the following individual parts:

Locking plate/locking disk

Spring blocking device/locking spring

Locking holder/locking body

Diode holder/diode holder

Diode

Head R60/head for Luer plug

The parts are arranged as follows:

The diode is inserted in the diode holder and fixed from behind with theESD bar. The diode is now seated in the diode holder. The diode isoriented over the interior diameter of the diode holder. Now the lockingholder can be pushed onto the diode. The locking holder is positionedover the interior diameter of the diode holder. The O-ring in thelocking holder absorbs minor shocks in the longitudinal direction.

The locking spring is inserted into the groove of the locking plate.This arrangement is placed into the opening of the locking holder. Thehead is pushed over the locking holder and the diode holder.

Functional Description:

The light conductor is inserted into the light conductor path via the1.5 mm bore in the head. After approx. 7 mm, the light conductor ispositioned via a decrease in the diameter to 1.1 mm. The light conductoris then pushed to the locking plate.

The locking plate is pressed onto the interior edge of the lockingholder by the pre-stress of the spring. The plate is always uncenteredby this and covers the 1.01 mm bore in the locking holder so that noradiation can exit.

The light conductor strikes the cone of the locking plate and pressesthe latter against the spring force into the center of the lockingholder. After the locking plate has been centered, the 1.01 mm bore ofthe locking holder is uncovered and the light conductor is pushedthrough this opening into the coupling area. The light conductor hasreached the coupling area when the Luer plug reaches the stop on thehead.

When the light conductor is withdrawn, the locking spring returns theplate to the non-central position, re-closing the 1.01 mm bore.

Discussion about the Safety of the Locking Mechanism

The spring wire in the locking spring has a diameter of 0.25 mm. Thegroove is 0.3 mm. Since the wire has a round shape, it cannot becomejammed in the groove. This means the blocking device is reliable. Theedges of the locking plate are broken by slide grinding to 0.2 mm.

The spring always presses the locking plate outward. There is evenlocking without the locking spring due to the position of the laserduring operation. The locking plate is pulled downward by its weight,closing the 1.01 mm bore. Because of the special shape of the spring, itis also not possible for the spring to jump out of the groove. The shapeof the spring encloses the locking plate and then secures it.

Because of the slight angle, any incline in the plate has no effect onthe locking mechanism. The plate moves back to its position the nexttime the light conductor is inserted.

Soiling on the locking mechanism has no effect on the function of thelock. The only factor that has to be taken into account is the dust fromwear in the light conductor. A simple cleaning of the mechanism can beperformed during the annual examination.

The only foreign bodies than can occur are 1.1 mm in size, since this isthe limiting size for the bore in the head.

Any reduction in the spring force is monitored using tests. Changescaused by falls to the ground are also monitored.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not as restrictive. The scope of the invention is, therefore,indicated by the appended claims and their combination in whole or inpart rather than by the foregoing description. All changes that comewithin the meaning and range of equivalency of the claims are to beembraced within their scope.

1. An arrangement for reducing microorganisms in response to appliedlight and a light-activated substance, comprising: a radiation devicecomprising a light blocking device, a laser source, a housing tube and ahead part having an anterior end part configured as a first connectorbody which is couplable to the laser source, the laser source generatinglight along a light path at a wavelength corresponding to an activationwavelength of the light-activated substance; a disposable, single-useapplicator, the applicator comprising a second connector body and alight conductor, the first and second connector bodies corresponding toone another and being engageable with one another by the anterior endpart of the head part engaging with the second connector body, the lightconductor having a first end couplable to the laser source by engagementof the anterior end part of the head part with the second connectorbody, the light conductor having a second end serving as a light exitarea out of which the generated light may be emitted to be applied ontoa microorganism-containing area onto which the light-activated substancehas been applied; wherein a battery for supplying current to electronicsfor the laser source is provided in said housing tube; wherein said headpart has a central bore for receiving and centering the first end of thelight conductor; wherein the light conductor has a numerical aperturegreater than 0.5; and wherein said blocking device has a firstconfiguration in which said light path is interrupted and a secondconfiguration in which said light path is not interrupted, said blockingdevice being in the first configuration when the applicator is notproperly coupled to the laser source, said blocking device being in thesecond configuration when the applicator is properly coupled to thelaser source.
 2. The arrangement in accordance with claim 1, whereinsaid blocking device contains a locking body securely connected to saidradiation device and with a hole arranged in said light path and whereina locking disk that is arranged movably with respect to said lockingbody interrupts said light path by blocking the hole as long as saidapplicator is not connected to said radiation device, and whereby aftera connection between said applicator and said radiation device iscreated the locking disk moves so as no longer to block the hole andinterrupt said light path from said laser source to said light conductorof said applicator.
 3. The arrangement in accordance with claim 1,wherein said light conductor has a numerical aperture greater than 0.7and/or wherein said light from said laser source is coupled directlyinto said light conductor of said applicator.
 4. The arrangement inaccordance with claim 1, wherein said light conductor has a definedgeometry of the light exit area that matches the light exit to the shapeof sites to be irradiated and produces either a two-dimensional orthree-dimensional radiation area, and/or wherein said light conductorhas at its second end a spacer that indicates an active light cycle andestablishes the correct irradiation distance.
 5. The arrangement inaccordance with claim 1, wherein said light conductor has a geometrythat permits narrow cavities and pockets of tissue with complex shapesto be penetrated and opened gently, or wherein said light conductor hasa conical tip with an angle of 1.5 to 4° to the perpendicular.
 6. Thearrangement in accordance with claim 1, wherein said light conductor hasa light exit surface that is provided with a predeterminedmicrostructure thereby to obtain enhanced scattering of light.
 7. Thearrangement in accordance with claim 6, wherein the microstructure isdimensioned in a range 10 μm to 200 μm.
 8. The arrangement in accordancewith claim 1, wherein said second connector body is a plug-in orscrew-in connector with a stop.
 9. The arrangement in accordance withclaim 1, wherein said light conductor passes through said secondconnector body and the light conductor first end projects rearward fromsaid second connector body at a predetermined length and when connectedwith said radiation device engages said head part thereof.
 10. Thearrangement in accordance with claim 1, device wherein the anterior endpart of the housing tube is configured as the head part of said firstconnector body, and a posterior end part of the housing tube isdetachably connected to a cap via a thread connection.
 11. Thearrangement in accordance with claim 1, wherein said housing tube, at ananterior end part thereof, is provided with the laser source and anelectronic board having a button actuateable from outside.
 12. Thearrangement in accordance with claim 1, wherein said housing tube ismade of metal and configured as a protective housing.
 13. Thearrangement in accordance with claim 1, wherein said housing tube, at aposterior end part thereof, is provided with a battery or an accumulatorfor supplying current to electronics on an electronic board and to thelaser source.
 14. The arrangement in accordance with claim 1, whereinthe laser source is arranged at said housing tube and is configured as alaser diode and situated at an anterior end part of the housing tube,and the light from the laser source is coupled to the applicator withdirect light coupling or light coupling via an optical system.
 15. Thearrangement in accordance with claim 1, wherein said housing tube, at aposterior end part thereof, is provided with a cap having a key-operatedswitch by means of which the radiation device is turned on and off. 16.A method of reducing microorganisms in response to applied light and alight-activated substance by using the arrangement of claim 1,comprising: applying the light-activated substance in an initialconcentration higher than a predetermined optimal concentration to anarea in which microorganisms are to be reduced; rinsing said area with amedium which reduces said initial concentration to the predeterminedoptimal concentration; wherein the predetermined optimal concentrationis a concentration at which, upon application to the area of light fromthe laser source, damage to the microorganism is optimized; blocking,with the light blocking device configured in the first configuration,said light path of light generated by the laser source; coupling thedisposable, single-use applicator to the laser source; in response tosaid coupling, configuring the light blocking device into the secondconfiguration in which said light path is unblocked; and emitting thegenerated light from the second end of the light conductor as saidapplied light onto said area to which the light-activated substance hasbeen applied.
 17. The method of claim 16, where said light-activatedsubstance comprises a solution of a photosensitizer in a solvent and theinitial concentration thereof in weight per volume is greater than 0.1%.18. The method of claim 17, wherein said initial concentration is atleast 1%.
 19. The method of claim 17, wherein said initial concentrationis not greater than 10%.
 20. The method of claim 17, wherein saidphotosensitizer solution initially has an acidic pH and said rinsingmedium is highly alkaline.
 21. The method of claim 17, wherein saidrinsing medium has at least one of the following three characteristics:an oxygen partial pressure; enrichment with molecular oxygen; enrichmentwith a peroxide.
 22. The method of claim 16, wherein, prior toirradiation of said area by said arrangement, a quantity of thephotosensitizer solution applied to the area is reduced by at least oneof wiping, dabbing, suctioning, or blowing.
 23. The method of claim 21,wherein said oxygen partial pressure is 4-6 mg/L and said enrichmentwith molecular oxygen is up to 14 mg/L.